National Cancer Institute

at the National Institutes of Health

Adjustment to Cancer: Anxiety and Distress (PDQ®)

Health Professional Version

Table of Contents

Overview

Studies examining the prevalence of mental disorders in cancer [1,2] show that
most cancer patients do not meet the diagnostic criteria for any specific
mental disorder; however, many patients do experience a variety of difficult
emotional responses.[3]

Psychosocial distress exists on a continuum (see figure below) ranging from normal
adjustment issues through the adjustment disorders of the fourth revised edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV-TR);[4] to a level close to, but below, the
threshold (i.e., meets some diagnostic criteria but not all) of diagnosable
mental disorders; to syndromes that meet the full diagnostic criteria for a
mental disorder (e.g., major depressive disorder). This summary focuses
primarily on the less severe end of this continuum: the normal adjustment
issues, psychosocial distress,[5] the adjustment disorders, and cancer-related anxiety. (Refer to the
PDQ summaries on Depression and Cancer-Related Post-traumatic Stress for more information.)

Anxiety is often manifested at various times during cancer
screening, diagnosis, treatment, or recurrence. It can sometimes affect a
person’s behavior regarding his or her health, contributing to a delay
in or neglect of measures that might prevent cancer.[6-8] For example, when
women with high levels of anxiety learn that they have a genetically higher level of risk of breast cancer than they had previously believed, they might
perform breast self-examination less frequently.[9]

For patients undergoing cancer treatment, anxiety can also heighten
the expectancy of pain,[10-12] other symptoms of distress, and sleep
disturbances and can be a major factor in anticipatory nausea and vomiting.
Anxiety, regardless of its degree, can substantially interfere with the quality
of life of patients with cancer and of their families and should be evaluated
and treated.[13-15]

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

Definitions

To effectively match patient needs with treatment
interventions, health care professionals must be able to distinguish the
periodic difficulties that characterize normal adjustment from more serious
mental disorders. To assist in this evaluation, health care professionals should understand the distinctions among a variety of related concepts, as defined below.

Normal adjustment: Adjustment or psychosocial adaptation to cancer has been defined [1-5] as an
ongoing process in which the individual patient tries to manage emotional
distress, solve specific cancer-related problems, and gain mastery or control
over cancer-related life events. Adjustment to cancer is not a unitary, single
event but rather a series of ongoing coping responses to the multiple tasks associated with living with cancer. (Refer to the Normal Adjustment section of this summary for more information.)

Psychosocial distress: Distress has been defined as “an unpleasant experience of an emotional, psychological, social, or spiritual nature that interferes with the ability to cope with cancer treatment. It extends along a continuum, from common normal feelings of vulnerability, sadness, and fears, to problems that are disabling, such as true depression, anxiety, panic, and feeling isolated or in a spiritual crisis.”[6,7] (Refer to the Psychosocial Distress section of this summary for more information.)

Adjustment disorders: The adjustment disorders, a diagnostic category of the fourth revised edition of the American Psychiatric
Association’s Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR),[8] are defined as reactions to an identifiable psychosocial stressor
(e.g., cancer diagnosis) with a degree of psychopathology that is less severe
than diagnosable mental disorders such as major depressive disorder or
generalized anxiety disorder and yet are “in excess of what would be expected”
or result in “significant impairment in social or occupational functioning.”
(Refer to the Adjustment Disorders section of this summary for more information.)

Anxiety disorders: Anxiety disorders are a group of mental disorders whose common symptoms include excessive anxiety, worry, fear, apprehension, and/or dread. Although some anxiety can be adaptive—particularly in response to stressors such as cancer—anxiety disorders are excessive, unwarranted, often illogical fears, worry, and dread. The DSM-IV-TR includes generalized anxiety disorder, panic disorder, agoraphobia, social anxiety disorder, specific phobia, obsessive-compulsive disorder, and post-traumatic stress disorder as types of anxiety disorders.[8] (Refer to the Anxiety Disorders: Description and Etiology section of this summary for more information.)

The distress continuum. Psychosocial distress exists on a continuum that ranges from normal adjustment issues to syndromes that meet the full diagnostic criteria for a mental disorder.

Risk Factors: Prevalence and Predictors of Distress

A few studies have investigated the prevalence of distress as measured by the National Comprehensive Cancer Network Distress Thermometer (DT).[1-6] Prevalence rates in patients with cancer range from 22% to 58%. Different cutoff scores have been used, with most studies using a cutoff score of 4 or 5.

Pooled results from multiple studies suggest that approximately 40% of cancer patients report significant distress.[7] Patients with lung, pancreatic, and brain cancers seem more likely to report distress, but in general, type of cancer is only modestly associated with distress.

In regard to prevalence of distress along the clinical course, one study of 236 newly diagnosed breast cancer patients (awaiting their initial consultation with a surgical oncologist) found that 41% reported distress scores higher than 5 on the DT. In this same group of women, 11% reported symptoms suggestive of major depression, and 10% reported symptoms of posttraumatic stress.[8]

In a study of 321 women with newly diagnosed stage I to stage III breast cancer, the ability of the single-item DT to specifically predict depression—as measured by a self-report questionnaire of the nine symptoms for major depressive disorder in the fourth revised edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV-TR)—was investigated. Sensitivity and specificity characteristics were evaluated, and the optimal cutoff score of 7 was identified, resulting in a sensitivity of 0.81 and a specificity of 0.85 for detecting depression. Therefore, individuals scoring 7 or above should undergo a more thorough psychosocial evaluation.[9]

Regarding predictors of distress, in a large sample (N = 380) of patients with mixed cancer diagnoses, those reporting a score of 4 or higher on the DT were more likely to be women, to have poorer functional performance (self-reported Karnofsky Performance Scale), and to have reported (on the Problem List that accompanies the DT) problems with housing, dealing with children, dealing with partner, depression, fears, nervousness, sadness, worry, and 14 of 20 physical ailments.[2]

In regard to predictors of posttreatment distress, a longitudinal, observational study of 151 women with early-stage breast cancer found that physical symptoms and side effects experienced during treatment were predictive of posttreatment cancer-related distress, amounting to 6% of the total 24% of variance accounted for.[10] In addition, demographic variables associated with this posttreatment cancer-related distress included younger age, nonwhite racial status, and less formal education. Clinical variables associated with distress included having a mastectomy rather than lumpectomy, receiving hormonal treatment, and the presence of a diagnosable mental disorder at the time of recruitment into the study.

Screening and Assessment

Screening and assessment have been viewed as two distinct processes.[1,2]
Screening is a rapid method of identifying patients with psychosocial distress and is
typically conducted by non–mental-health professionals using brief self-report questionnaires to determine whether an individual needs referral
for more extensive assessment.[3] The psychosocial assessment of the cancer
patient is a more in-depth clinical interview focused on factors relevant to
coping and adaptation. Mental health professionals conduct the assessment
interview to determine how well a patient is adjusting.[1]

Various comprehensive cancer centers have developed models for screening for
psychosocial distress. Although there are notable differences, most models
involve the following sequential steps:

Screening administration.

Scoring and evaluation.

Referral.

Most screening for psychosocial distress focuses on the individual patient; however, some family-focused screening procedures are being developed.[4]

Administration of a screening instrument involves a 5- to 10-minute
process in which each patient answers a series of simple, straightforward
questions about distress, either orally or via a self-report paper-based questionnaire or
computer questionnaire. Answers are scored and evaluated on the basis of previously
determined criteria. If scores fall above the defined criteria, then a formal
referral to the appropriate discipline (social work, psychology, psychiatry,
palliative care, or pastoral care) is made. Distress management then begins with
a more comprehensive face-to-face psychosocial assessment interview [1] by a
qualified health care professional (e.g., social worker, psychologist,
psychiatrist, palliative care specialist, or pastoral counselor) appropriate to the issues identified.

The success of screening programs can be measured in terms of the following outcomes:

Accurate identification of patients who are experiencing significant psychosocial distress.

Decreased level of distress and improved quality of life resulting from the screening program.

Few empirical studies have evaluated the impact of structured screening programs using the outcomes above. Intervention in most of these studies included telephone follow-up of screening results with referrals or in-person discussions with clinicians, trained or untrained in screening. Study designs have differed in terms of screening tools (brief vs. comprehensive screening tools), intervention components (trained vs. untrained screening clinicians), and study outcomes. Study designs have also differed in their controls; for example, control groups in some studies did not undergo screening,[5] while others involved patient screening but with no screening results conveyed to clinicians.[6]

The results of the screening studies have been mixed, depending on the structure of the screening programs and the assessed outcomes. Two studies found no meaningful differences between control and intervention groups in distress, quality of life, or cancer needs.[5,6] Low patient acceptance of psychosocial referral services was one of the limitations identified in these studies.[6]

In one study, a subgroup of moderately to severely depressed patients showed a significant reduction in depression after the intervention,[6] while another study concluded that the best predictor of decreased anxiety/depression was referral to psychosocial services.[7] Another study showed feasibility of implementation of a personalized as well as a computerized screening program in a large patient population (N = 3,133) at a tertiary cancer center.[8]

Further empirical evaluation of the effectiveness of screening programs is necessary, given the mixed results to date. The following examples will help to illustrate the process.

Model Screening Programs

Memorial Sloan-Kettering Cancer Center has experimented with a distress thermometer (DT) modeled after those used to
measure pain.[9] The descriptive anchor points on the thermometer include the following:

"No distress" at a rating of 0.

“Moderate distress” at a rating of 5.

“Extreme
distress” at a rating of 10.

Patients are asked, “How would you rate your
distress today, on a scale of 0 to 10?” Accompanying the thermometer is a
problem list that helps identify relevant potential sources of stress. The patient is asked to check off the problems that are most relevant. Categories of problems include the following:

Practical (e.g., housing, insurance,
or transportation).

Physical (e.g., pain, nausea, or fatigue).

Family or support
(e.g., partner, children, or friends).

Emotional (e.g., worry, sadness,
depression, or anger).

Spiritual/religious (e.g., relating to God or loss of
faith).

The primary oncology team (oncologist, nurse, palliative care
specialist, and social worker) is responsible for administering and evaluating a
patient’s response to this brief screening and arranging for a referral, when
necessary. Preliminary testing of this procedure used a cutoff score of 5 or
higher as requiring further evaluation. Initial needs assessments have shown
that 20% to 35% of patients report significant levels of distress.

At Johns Hopkins Cancer Center, all new patients receive an 18-item version of the Brief
Symptom Inventory (BSI),[10] which lists 18 problems people sometimes experience
(e.g., feeling faint or dizzy, having no interest in things, loneliness, or nausea or
upset stomach). They are asked, “How much were you distressed by” each of the
18 problems “during the past 7 days including today?” The procedure is
automated and utilizes existing clerical and support staff to distribute and
retrieve the inventory during the first or second visit.[2] After computerized
scoring is completed, professional staff is involved when offers for services
are being provided. Patients screened as having high distress are referred to a
social worker for immediate follow-up; those screened as having low
distress are referred to the psychosocial orientation program, which is a structured educational program designed to enhance the adaptation of patients
by providing information about a range of psychosocial programs (e.g.,
disease-specific support groups or psychoeducational presentations).

The Oncology Symptom Control Research group at Community Cancer Care typically
screens all incoming patients with the Zung Self-Rating Depression Scale
(ZSDS).[11,12] The ZSDS is a 20-item self-report depression screen that has been
used to detect depression and more general distress; single items are also used
to screen for conditions such as fatigue.[13] Staff typically administer the
screen while patients are in the waiting room. Scores are analyzed immediately
after completion so that the medical oncologists can be briefed on any
pertinent issues. In addition, patients scoring in the moderate range or
higher are identified for further follow-up and more extensive interviews and
assessment by the staff psychiatrist or psychologist. Also, patients
who trigger single items of interest such as fatigue are interviewed and
monitored for possible inclusion in a number of symptom-control research trials.

Distress Thermometer

Although many screening instruments have been tested with cancer patients (see Table 1), the National Comprehensive Cancer Network (NCCN) DT has been the most widely investigated. The psychometric properties of the DT (a 0–10 visual analog scale, in the form of a thermometer labeled with “No Distress” at 0, “Moderate Distress” at the midpoint, and “Extreme Distress” at 10) have been investigated.[14]

The measure was found to have reasonable convergent and divergent validity when compared with two well-established, multidimensional symptom inventories. This very brief rapid-screening procedure has a moderate ability to accurately detect distress as defined by scores indicative of “caseness” on the two-symptom inventories. When specific cutoff scores were tested to maximize sensitivity and specificity, no single cutoff that maximized accuracy of classification was discovered. Thus, it was recommended that varying cutoff scores result in different referral recommendations, such that low scores result in no referral, moderate scores result in an optional referral, and high scores result in a strong recommendation for further interventions.[14]

Self-Report Screening Instruments

The NCCN single-item, rapid-screening instrument asks patients to rate their distress on a scale of 0 (“no distress”) to 10 (“extreme distress”). On an accompanying problem list, patients are asked to indicate what has been a problem for them in the past week. Studies [14-18] have tested the ability of the single-item measure to accurately identify patients in distress. In general, these ultrashort screening methods have demonstrated only modest overall accuracy. They are best for ruling out, but performed poorly at confirming, distress, anxiety, and depression.

Many other self-report questionnaires have been used as screening instruments (see Table 1); in general, they also are better for ruling out distress and perform poorly at confirming distress. Thus, most screening instruments will yield a high number of false-positive results and need to be followed by a more extensive psychosocial assessment interview.

Table 1. Examples of self-report Screening Instruments Used for Identification of
Psychosocial Distress in Cancer Patients

Self-report screening instruments must be scored, evaluated, and discussed with
each patient. Triage—the process of communicating screening results,
discussing each patient’s needs, and determining the best course of further
action—is key to the successful use of screening. In fact, screening without
availability of appropriate treatment resources is considered unethical. The primary oncology team (oncologist, nurse, palliative care specialist,
social worker, and counselor) is responsible for successful triage. In some
studies a significant percentage of patients who report moderate to high levels
of distress refuse further assessment.[26-29] Thus, it is important to
consider how the primary oncology team can introduce the need for further
psychosocial assessment.

The
NCCN standards of care [9] suggest distress rated as mild might result in a
referral to a local self-help group or management by the primary oncology team
only. Distress rated as moderate to severe warrants referral to other
appropriate professionals (psychologists, psychiatrists, social workers,
palliative care specialists, or pastoral counselors), depending on the nature of
the distress.

Psychosocial Assessment

The assessment of psychosocial adaptation should follow screening when distress is identified. The psychosocial assessment is typically a semistructured interview during which the professional evaluates how well an individual patient, a patient’s family, and other significant people in a patient’s life are adapting to the current demands of the illness. In general, this assessment process considers a wide variety of factors relevant to overall adaptation.[1] (Refer to the General Factors Influencing Adjustment section of this summary for more information.)

A successful transition from screening to assessment involves clear communication between the oncology team and the patient.
Although there is no single best way to talk to patients about psychosocial
needs, clinical experience suggests some important concepts. First, most
patients will respond to the recommendations of health care professionals who
exhibit trust, expertise, warmth, care, and concern.

Choice of words is important. Words that suggest the stigma of serious mental
illness, such as psychiatric, psychological, mental disorder, maladjustment, or mental illness, should be avoided—in favor of words such as distress, concerns, worries, uncertainties, or stressors from the illness or its
treatment. Suggestions for word choice include the following:

The questionnaire you filled out helps us to understand you as a whole
person, and we want to provide the best care possible for you—physically,
emotionally, socially, and spiritually.

As you may realize, a serious illness can affect the quality of your life
in many ways (emotionally, socially, work, relationships, finances,
energy). There is much more to this illness than just the physical, and
we want to be sure we are addressing these other dimensions of your life.

Your concerns and worries are very understandable, given your illness and
its treatment. We don’t want to ignore the (emotional, social, spiritual)
aspects of your experience right now.

We have found that many patients benefit greatly from a chance to talk
further about their concerns with a (social worker, mental health
professional, palliative care specialist, or pastoral counselor), and we
would like to schedule that for you.

For further explanation, we suggest an interview that lasts about 45 minutes with a professional who will:

Listen closely to you.

Want to know about your experiences with your illness.

Ask about you, your family and friends, and other support persons.

Ask about how you have been adjusting to your illness and may
encourage you to continue (and give you feedback about) successful
coping strategies you are already using.

Normal Adjustment

Adjustment or psychosocial adaptation to cancer has been defined [1-5] as an
ongoing process in which the individual patient tries to manage emotional
distress, solve specific cancer-related problems, and gain mastery or control
over cancer-related life events. Adjustment to cancer is not a unitary, single
event but rather a series of ongoing coping responses to the multiple tasks associated with living with cancer. Patients are faced with many challenges that vary
with the clinical course of the disease. Common periods of crisis and
significant challenge include the following:

Each of these events has certain coping tasks, particular
existential questions, many common emotional responses, and specific problems.

Normal or successful adjustment is indicated in patients who are able to
minimize disruptions to life roles, regulate emotional distress, and remain
actively involved in aspects of life that continue to hold meaning and
importance.[5]

Coping refers to the specific thoughts and behaviors a person uses in his or
her efforts to adjust.[2] Coping style refers to the most common, more
frequent, and longer-term style of coping that an individual tends to use
across a variety of life situations. One’s coping style is often closely
related to one’s overall disposition and personality (e.g., optimism,
pessimism, introversion, extroversion).[7]

Coping strategies refer to those less frequently used and more
situation-specific coping efforts, such as readjusting one’s daily routine or
work schedule to adjust to the side effects of cancer treatment.
Coping strategies comprise efforts to adjust. Although there are many
successful coping strategies, three broad categories have been noted:[2,8-10]

Problem focused.

Emotion focused.

Meaning focused.

Problem-focused
strategies help patients manage specific problems by directly trying to alter
problem situations. Emotion-focused strategies help a person regulate his or
her degree of emotional distress. Meaning-focused strategies help patients
understand why this has happened and what impact cancer will have on their
life. In general, persons who adjust well typically remain committed and
actively engaged in the process of coping with cancer and continue to find
meaning and importance in their lives. Conversely, persons who do not adjust
well often become disengaged, withdraw, and feel hopeless. Thus, assessing the
degree of engagement versus giving up may be a way to distinguish between
successful and unsuccessful adjustment.[5]

For example, in a correlational study of adolescent cancer patients and their parents, engagement coping by the adolescent (including cognitive restructuring, seeking social support, expressing emotions, and problem solving) was associated with lower levels of distress. Conversely, disengagement coping by parents (including problem avoidance, wishful thinking, social withdrawal, and self-criticism) was associated with increased distress.[11]

In a prospective investigation of different types of problem-focused coping strategies, 146 women with early-stage breast cancer were studied. Study results showed that a strategy of concentrating on symptoms, measured at the end of treatment, was predictive of less improvement in physical and mental quality of life at 6 months' follow-up, while a strategy of information seeking was associated with greater improvement in physical quality of life. These findings suggest that problem-focused coping consists of a variety of specific coping strategies—only some of which may be beneficial to quality of life.[12]

One criticism of the literature on coping with cancer focuses on the assumption that “coping with cancer” is a single unitary event. In reality, coping with cancer involves coping styles and strategies that may differ and vary according to the nature of the stressors being encountered. For example, in a study of 52 adults receiving palliative care for cancer,[13] patients participated in a semistructured interview during which they were asked how they coped with their most significant stressors. Three stressor domains were identified:

Social

Physical

Existential

Three categories of coping were also identified:

Problem focused

Emotion focused

Emotion-focused avoidance

Results showed that most participants used a range of coping strategies; however, there were interactions between stressor domains and coping categories. Problem-focused strategies were used less frequently for the existential stressors, while emotion-focused strategies were used less frequently for the physical stressors.[13]

Coping Theory

One cognitive theory of coping [14] proposes that in response to significant
life events, a person asks two important questions:

Is this event personally
significant to me?

What resources do I have to manage/control this
event?

When an event is perceived to be of personal significance (nearly all
cancer-related life events would be), and when one’s personal resources
are perceived to be inadequate to the demands of managing the event, distress
can occur. One way to conceptualize the amount of distress experienced by
patients is the balance or ratio between perception of the demands that a
situation (e.g., chemotherapy) places upon them and perception of the resources
they possess (e.g., effective antiemetics) to effectively manage these
demands:

Distress = Perceived Demands/Perceived Resources

Individuals with the same diagnosis or treatment regimen may experience very
different levels of distress. A high level of distress could result from an
individual’s perceptions that either the demands of a situation are very high
or his or her resources are very low (or both). Conversely, low distress is
the result of a perception that either the demands of a situation are very low
or the individual’s resources are high.[15] To lower distress, therefore,
either the perceived demands of the situation should be lowered, or the
perceived resources should be increased.

General Factors Influencing Adjustment

Although there are some commonalities in normal adjustment to the varying
stressors of cancer, there are also many individual differences. It is
difficult to predict how individuals will cope with cancer, so it is important
to recognize factors that influence adjustment to cancer. One study of women with stage II or III breast cancer [16] reported that higher levels of stress measured postsurgically at the time of diagnosis predicted lower physical and psychological quality of life. The stress measures included the following:

Another study evaluated women with stage 0 breast cancer to stage III breast cancer (N = 89) at three time points: during treatment, at 3 weeks following end of treatment, and at 3 months posttreatment. Most survivors showed good adjustment on general distress indices. The factors predicting sustained distress included young age, history of depression or anxiety, and more extensive treatment. Younger age was the only factor that predicted greater distress across all evaluated measures.[17]

Psychosocial
adjustment/adaptation has been determined to be influenced by three broad
categories of factors: cancer derived, patient derived, and
society derived.[4,18] Cancer-derived factors include the following:

Type of cancer.

Cancer stage.

Prognosis.

Where a patient falls in the cancer
continuum of diagnosis, treatment, and recurrence.

Patient-derived factors also include consideration for stage of life [22] (i.e.,
developmental tasks—young adults may respond quite differently compared with older
adults).

Society-derived factors include the general societal views of cancer
(e.g., stigma), as well as the influence society has on issues such as
availability of treatments, open versus closed discussion of the illness, and
popular beliefs about cause.

The personality traits of optimism and pessimism might play a critical role in the psychological well-being of cancer patients. A German study investigated the impact of optimism and pessimism on psychological well-being in 161 newly diagnosed cancer patients with heterogeneous cancers.[23] Patients were assessed for optimism/pessimism and positive/negative emotions before the start of their first chemotherapy session and at 9 months' follow-up. Before the start of chemotherapy, psychological well-being was associated with higher optimism and lower pessimism. Only pessimism predicted negative change in psychological well-being at the 9-month follow-up. Additionally, only pessimism predicted heightened perception of chemotherapy-related side effects.

The availability of social support, as part of a social network, has been found to be related to mortality from breast cancer. In a longitudinal study of 2,835 female nurses with breast cancer, those who, before diagnosis, reported no close contacts (e.g., relatives, friends, or living children) had a twofold increased risk of mortality from breast cancer, compared with those who had more social contacts (e.g., ten or more close relatives). This increased mortality was only found when comparing these two extremes in social ties, suggesting that women with relatively few social contacts or an intermediate number of contacts may not be at increased risk. Overall, these results suggest the important role of close relatives willing to step in and provide needed care.[19]

Situation-Specific Influences on Adjustment

Hearing the diagnosis

The process of adjusting to cancer can begin even before a diagnosis. Patients
may respond with normal levels of fear, worry, and concern when they have
unexplained symptoms or when they realize that they are undergoing testing to
determine the presence of cancer. When they hear the diagnosis, their fears
become realized, generating a psychological and existential plight
(crisis).[24] Many people wonder, “Could I die from this?”

Receiving a diagnosis of cancer results in a crisis that includes expected and
normal emotional distress. One author [25] has described the normal responses
to the crisis of cancer as consisting of three phases:

Initial response.

Dysphoria.

Adaptation.

Phase I, the initial response, consists of disbelief, denial, and shock that
the news is true. Some patients will attempt to prove that the diagnosis is
not true (“Are you sure you have the right test results?”). Most patients will
report a period of disbelief accompanied by an inability to clearly process
information. They may feel numb or in shock, or as if, “This can’t be happening
to me.”

Such a high level of distress can be problematic because many times,
immediately after informing patients of their diagnosis, physicians outline the
treatment options. Under these emotional circumstances, many patients may be
unable to understand or remember this important information. Thus, the
presence of others or other means of being able to review the information can
be extremely important (e.g., tape recording the discussion about the treatment
plan or providing a second appointment at a later date, specifically for
reviewing the treatment plan). Although there are many individual differences,
this initial response of disbelief, denial, and shock usually lasts about a
week in patients who adjust well.

Phase II, dysphoria, consists of a variable period of time (but usually lasting
1–2 weeks) during which the patient is slowly acknowledging the reality of the
diagnosis. During this time patients will typically begin to experience a
significant degree of distress in the form of depression, anxiety, insomnia,
anorexia, poor concentration, and varying degrees of inability to function in
daily roles. Intrusive thoughts of illness and death may occur very often and
seem to be uncontrollable.

As more information about treatment options is
provided, correctly processed, and understood, feelings of hope and optimism
begin to emerge more frequently through the dysphoria. Distress levels can be elevated for newly diagnosed patients awaiting surgery. Additional professional support to address problems such as fatigue, insomnia, and depressed mood can be helpful during this time.[26]

Phase III, longer-term adaptation, consists of the extended time during which
more long-lasting and permanent adjustment occurs. This period consists of
weeks and months. During this period, patients are utilizing a variety of
coping strategies and styles.[9] Coping styles are longer-term, established
ways for coping with many previous life events; coping strategies are
situation-specific efforts to resolve particular cancer-related situations.
This combination of longer-term coping styles and short-term coping strategies
usually serves patients well in their efforts at adaptation. There is no single best way to cope. The individual differences
patients bring to their encounters with cancer will result in varied coping
styles and strategies.[5]

Active cancer treatments

During the active treatment phase of the illness, a patient’s adjustment is
focused primarily on coping with the many and varied stressors of treatment.
These may include apprehension and fears about:

Disruptions to
daily life (including changes in life roles—for example, the breadwinner who can no longer work).

Patients who
adjust well are able to tolerate these short-term stressors via a cost-benefit
approach in which they weigh the discomforts of short-term loss against the
benefits of long-term gains (e.g., increased survival) and conclude, “It is
worth it.”[25] Questions that often occur during active treatment include the following:

Will I survive this?

Will they get all of the cancer?

What side effects will I
experience?

As these and related questions arise, patients utilize coping
styles and strategies to adapt. Although many different coping strategies are
useful during this phase, problem-focused coping—strategies designed to manage
specific problem situations (e.g., fatigue, transportation to treatments,
altered work schedules, and role changes)—are often utilized.

Posttreatment

Before active treatments are completed, most patients look forward to the
conclusion of treatment with positive anticipation and hopes of returning to
normal. However, the completion of active treatment can be a time of great
ambivalence for cancer patients and their families. The completion of
treatments suggests a time of celebration and relief, yet it can also be a time
of heightened distress, with a renewed sense of vulnerability that comes with
the cessation of active medical efforts to fight the disease.[27]

Those who
adjust well are able to balance their positive expectations with the realities
of ongoing fears and apprehensions. Many patients report enhanced anxiety and
worry related to fears of recurrence and decreasing frequency of medical
surveillance via less frequent physician contacts. Other adjustment issues
include living with uncertainty, returning to previous life roles, and
hypervigilance to health concerns.[6]

During remission, patients begin a
sequence of regular follow-up appointments with their oncologist. Normal
anxiety and worry often intensify as the dates of follow-up appointments
approach. Normal anxiety comes from concerns about recurrence and the related
emotional consequences (e.g., re-entry into the patient role and renewed
feelings of loss of control).[28] Many patients find waiting for test results
to be a particularly distressing experience.

In one of the few empirical studies of posttreatment adjustment, 94 women with stage 0, I, II, or III breast cancer who were completing radiation therapy were assessed on measures of depression, anxiety, and quality of life on the last day of treatment and at 2 weeks, 4 to 6 weeks, 3 months, and 6 months posttreatment. Results found elevated symptoms of depression, low-level anxiety, and diminished quality of life on the last day of treatment; however, by 2 weeks later, symptoms of depression decreased significantly, and quality of life improved significantly. No other significant changes were found at any of the later posttreatment time periods, suggesting improvements in depression and quality of life occur quickly in most patients.[29]

Normal adjustment to posttreatment and remission involves utilization of a
variety of coping strategies; however, this phase often involves the frequent
use of emotion-focused coping strategies (those designed to help regulate the
normal emotional distress), given the variety of ambivalent emotional
reactions. Those who adjust well are more likely to be comfortable expressing
a wide range of both positive and negative emotions. Emotion-focused coping
strategies include the following:

Honesty with one’s emotions.

Awareness of one’s
feelings.

Nonjudgmental acceptance of one’s feelings.

Ability to
articulate these feelings to others.

Willingness to approach the task of
working through these emotions.

Availability of support from others willing
to listen and accept.

Recurrence

The transition from a curative treatment plan to one of palliative care is
extremely difficult for cancer patients.[25] Extreme anguish often accompanies
this transition as the patient faces renewed psychological distress, physical
symptoms, and the existential crisis of death, all of which combine to result
in the suffering often associated with advanced cancer.[30]

The normal adjustment to this crisis is characterized by initial shock,
disbelief, and denial followed by a period of significant distress (e.g.,
depressed mood, difficulty concentrating, frequent intrusive thoughts of
death). Normal adjustment may include the following:

Periods of significant sadness and
crying.

Periodic feelings of anger at God or one’s perceived higher power.

Periods of withdrawal and isolation.

Thoughts of giving up.

However,
as with the initial diagnosis, this distress is often followed by a gradual
adjustment over a period of weeks. It is important to note that these common
reactions do not necessarily indicate psychopathology. Although the intensity
of these emotions might be similar to more severe psychopathology, their
frequency of occurrence and duration tend to be shorter. Patients experiencing
normal adjustment to recurrence and palliative care will typically rally from
these strong emotions more quickly than those experiencing a true mental
disorder. (Refer to the PDQ summaries on Depression and
Cancer-Related Post-traumatic Stress for more information.)

Adjustment to recurrence and palliative care often involves shifting
expectations from cure to healing. From this perspective, healing involves a
process of becoming whole again,[31] of transforming one’s life in a variety
of ways in the face of death. This process of adjustment involves maintaining
hope, which is viewed as crucial in overall adaptation to crisis.[32]

The
patient who successfully adjusts to the crisis of recurrence often shifts
expectations and maintains hope in a variety of meaningful life activities.
For example, a patient who has confidence that pain and suffering can be
controlled will have hope for future quality of life. Patients who
believe they are loved and cared for will have hope in their future
relationships. Religion and spirituality play a very important role in helping
many patients maintain hope. Religion or spirituality can provide a belief
structure that helps in coping with the crises of recurrence. During
recurrence and palliative care, patients are likely to utilize meaning-based
coping strategies and are likely to seek comfort in prayer and in their
religious practices/rituals or spiritual beliefs. In addition, one study suggests that prognostic awareness in combination with inner peace is associated with better mental health and quality of death outcomes for patients with advanced cancer and for their surviving caregivers during bereavement.[33]

In a study of women with recurrent breast cancer, significant impairments in physical, functional, and emotional well-being were found within 1 month after recurrence; however, a patient’s self-efficacy (confidence in his or her ability to manage the demands of illness), social support, and family hardiness (family’s internal strength and ability to manage hardship and change) had positive effects on quality of life. Conversely, more distress about physical symptoms, additional life concerns, a sense of hopelessness, and a negative perception of illness or caregiving were associated with a lower quality of life.[34]

Survivorship

The adjustment from posttreatment to long-term survivorship is
gradual and extends over many years. However, most patients, despite various
cancer diagnoses and treatments, adjust well,[3] with some even reporting
benefits to a cancer diagnosis (e.g., greater appreciation of life,
reprioritizing of life values, strengthening of spiritual or religious
beliefs).[35-38] Patients who have poorer adjustment tend to have greater
medical problems, fewer social supports, poorer premorbid psychological
adjustment, and fewer economic resources.[3]

As cancer treatments have improved, cancer is becoming a chronic illness,
particularly with certain cancer types (e.g., prostate, breast). Each of the
various psychosocial areas of functioning with a chronic illness has its own
unique adjustment issues. For example, long-term adjustment to being a
survivor of cancer involves considerations of how one adjusts psychologically,
socially, sexually, vocationally, and, of course, physically.

In general, studies of cancer survivors and healthy comparison groups have
found no significant differences in measures of psychological distress, marital
and sexual adjustment, social functioning, and overall psychosocial
functioning.[3] However, there are some common areas of distress experienced
by many cancer patients that are subthreshold or not severe enough to meet
diagnostic criteria. These may include the following:[3,39]

In one of the few prospective longitudinal studies of cancer survivors, 752 patients from three U.S. states were asked about a variety of psychosocial problems. About 1 year after diagnosis, 68% were concerned with their illness returning, approximately 60% were worried about recurrence, and 58% had fears of the future. In addition, approximately two out of three survivors were concerned about a physical health problem such as fatigue and loss of strength. Approximately 48% reported concerns with sleep difficulties, and 48% reported concerns with sexual dysfunction. Younger survivors (aged 18–54 years), women, nonwhites, unmarried survivors, and those with lower incomes reported more problems. In comparisons of four common cancers, the most concerns regarding problems in living were reported by those with lung cancer, followed by survivors of breast, colorectal, and prostate cancers.[40]

A large (N = 660) longitudinal study of women breast cancer survivors older than 65 years investigated factors associated with changes in emotional well-being. The overall findings suggest that the 5-year survivorship experience for most women is relatively stable, with few changes in emotional well-being. However, it was noted that women who had fewer than 12 years of formal education and women who perceived themselves as “never being cured” were more likely to experience declines in emotional well-being, while those who had better physical functioning, good emotional support, and the perception of positive physician-patient communication were less likely to have poor emotional health.[41]

Psychosocial Distress

Distress has been defined as “an unpleasant experience of an emotional, psychological, social, or spiritual nature that interferes with the ability to cope with cancer treatment. It extends along a continuum, from common normal feelings of vulnerability, sadness, and fears, to problems that are disabling, such as true depression, anxiety, panic, and feeling isolated or in a spiritual crisis.”[1] Standards of care have been
developed for the management of psychosocial distress.[2]

The National Comprehensive Cancer Network [1] has the broad goal of
establishing standards of care so that all patients experiencing psychosocial
distress will be accurately and routinely identified, recognized, and treated.
These guidelines include recommendations for the following:

Screening.

Triage.

Initial evaluation.

Also included are referral and treatment guidelines for each participating profession:

Mental health (psychology and psychiatry).

Social work.

Palliative care.

Pastoral care.

The times most likely to require screening include the following periods during the illness when distress is most likely to occur:

Psychosocial Interventions for Distress

The efficacy of psychosocial interventions in adult cancer patients is supported by an extensive literature.[3][Level of evidence: IV];[4-6][Level of evidence: I] Reviews have concluded that, in general, psychosocial interventions for cancer patients have shown positive benefits.

Psychosocial interventions have generally been defined as nonpharmacologic interventions that include a variety of psychological and educational components. Typical components include the following:

Relaxation training.

Cognitive and behavioral coping strategies.

Cancer education/information sessions.

Group social support.

Interventions have included various combinations of these components, have varied in length (single session to multiple weekly sessions), and have been administered in both individual and group formats. The most common patient population has been U.S. white women of middle to higher socioeconomic status who have breast cancer; however, some studies include mixed cancer diagnoses, and studies from European countries have appeared.[3] Outcome measures have varied and have included the following:[3,4]

Emotional adjustment (e.g., depression, anxiety).

Functional impairment (e.g., return to work, social roles).

Disease-related symptoms (e.g., nausea/vomiting, fatigue, pain).

Health behaviors (e.g., diet, smoking, exercise).

Immune system functioning.

A biobehavioral model [3] hypothesizing psychological, behavioral, and biologic pathways from cancer stressors to disease outcome has guided much of this research; however, the most common outcome measured has been emotional adjustment.

Although positive benefits have been found, their clinical significance has been questioned. Reviewers have offered varying conclusions regarding the size of these positive effects,[4][Level of evidence: I] ranging from negligible for depression, to small for overall emotional outcomes, to moderate for anxiety.[5][Level of evidence: I]

Effect sizes may be related to the timing of the intervention and patient selection procedures. For most patients, levels of psychosocial distress are highest during the earliest days of their cancer experience and, for many, dissipate quickly. Thus, if interventions are offered later in the cancer experience (weeks or months after diagnosis and treatment), patients may be experiencing less distress than they would have experienced if interventions had been offered earlier, making large effects more difficult to detect.[7][Level of evidence: II]

In one study,[8] 249 breast cancer patient-partner dyads were randomly assigned to one of four groups:

A control group that received standard disease management.

A standardized psychoeducation group.

A group that received telephone counseling.

A group that received psychoeducation plus telephone counseling.

Patients and partners who received the study interventions had less side-effect distress and severity as well as higher levels of psychological well-being than those who received standard care. In addition, the study results support the efficacy of low-cost, replicable interventions by video and telephone to achieve these physical and psychological benefits.[8]

These positive effect sizes indicate that the average patient receiving the intervention is better off than between 57% and 65% of those not receiving the intervention.

In summary, it appears that when psychosocial interventions are offered to patients who are found to be experiencing distress (e.g., anxiety, depression), the efficacy of the intervention is very strong. Thus, the overall positive benefit for psychosocial interventions seems to be greater with those who seem to need it most.[4,5]

Randomized trials of group interventions for breast cancer

The four studies described below are representative of randomized clinical trials testing the efficacy of small-group psychosocial interventions for U.S. women with early-stage breast cancer. Note that the studies vary in total treatment time, from 8 hours [9][Level of evidence: I] to 20 hours [7,10][Level of evidence: II] to 27 hours,[11][Level of evidence: I] and have a variety of intervention components.

Investigators tested the efficacy of a 10-week, 2-hours-per-week group cognitive-behavioral stress management intervention.[7] One hundred newly treated women with breast cancer were randomly assigned to either the intervention or to a control condition. The psychosocial intervention consisted of ten 2-hour group sessions during which didactic material was presented, intermixed with a variety of experiential exercises and homework assignments. The overall intervention focused on learning to cope better with daily cancer-related stressors. Topics included the following:

Progressive muscle relaxation with imagery.

Cognitive restructuring.

Interpersonal conflict resolution.

Assertion training.

Enhanced social support.

The control condition consisted of a day-long seminar in which participants received a condensed version of the intervention with significantly less time to interact within the group. Among intervention participants, results showed the following:

A decrease in depression.

No change in other measures of emotional distress.

An increase in “benefit finding” (i.e., reporting that having breast cancer had made positive contributions to their lives) and optimism.

In a larger (N = 199) randomized study conducted by the same research group [10] on women with stage 0 to stage III nonmetastatic breast cancer, an intervention similar to that in the first study produced somewhat greater sustained decreases in cancer-related intrusive thoughts and sustained improvements in anxiety.

Another study examined an 18-week, 1.5-hours-per-week group intervention consisting of psychological strategies designed to reduce stress, enhance mood, alter health behaviors (diet, exercise, smoking), and enhance adherence to cancer treatments.[11] Outcome measures included emotional distress, health behaviors, and immune responses. Two hundred twenty-seven women, all of whom had received surgery for regional breast cancer, were randomly assigned to either the intervention group or an assessment-only control group. Compared with the control group, the intervention group showed the following:

Immune responses in the intervention group were consistent with the psychological and behavioral changes. This study is a strong example of efforts to measure changes in a variety of biobehavioral (psychological, behavioral, immune) variables after a psychosocial intervention.

Other investigators evaluated an educational intervention consisting of 2-hour once-per-month group sessions for 4 consecutive months.[9][Level of evidence: I] Participants were 252 women younger than 50 years who had early-stage breast cancer, who had recently completed nonhormonal adjuvant treatment, and who were facing the transition from active treatment to posttreatment survivorship. They were randomly assigned to one of three groups:

A standard medical care group.

A nutrition education group.

A psychosocial education group.

The psychosocial and nutrition education groups included information dissemination, discussion, and some activities/exercises. Topics rotated monthly, and participants could join a group at any time (i.e., they were open groups). In general, patient-to-patient interaction was minimal because sessions were more didactic presentations. The psychosocial education group presented topics relevant to younger women with breast cancer, such as the following:

Talking with children about cancer.

How to carry on with life after a diagnosis.

Relationships/intimacy with partners.

Hormones and cancer.

Genetic bases of breast cancer.

The nutrition education group included information about choosing fruits, vegetables, and low-fat foods and how to consistently incorporate these foods into daily life. Shopping, low-fat cooking, eating out, and other related topics were presented. Results showed that patients in both of the intervention groups reported fewer depressive symptoms and better physical functioning at a 13-month follow-up. This study is an example of a more targeted intervention designed for a specific patient population (younger women with breast cancer) at a specific time in their treatment course (soon after completion of active treatment).

Problem-solving, focused, individual psychotherapy

A variety of individual psychosocial interventions have been studied. One study emphasized the development of problem-solving abilities.[13][Level of evidence: II] In this study, the psychosocial intervention consisted of ten 1.5-hour weekly individual psychotherapy sessions (either with or without a significant other present) that focused on training to become an effective problem solver. Four rational problem-solving tasks were emphasized that included skills in the following areas:

Better defining and formulating the nature of problems.

Generating a wide range of alternative solutions.

Systematically evaluating potential consequences of a solution while deciding on the optimal ones.

Evaluating the eventual outcome after solution implementation.

Between-session homework with tasks relevant to each step was assigned, and patients received a written manual and were encouraged to refer to it as problems arose. One hundred thirty-two adult cancer patients with mixed cancer diagnoses were randomly assigned to two treatment groups and one wait-list control. The two treatment groups included individual problem-solving therapy alone and problem-solving therapy with a significant other (e.g., spouse, friend, adult child) present.

Overall results showed that participants in the two treatment groups were more effective problem-solvers and experienced less psychological distress and improved quality of life. No differences between treatment groups were found.[13] In this example, an individual psychotherapeutic intervention designed to increase a patient’s problem-solving abilities was shown to result in a better quality of life and less psychological distress.

Self-administered stress management training for chemotherapy

In a randomized trial of 411 mixed-diagnosis cancer patients,[14][Level of evidence: I] traditional psychosocial care was compared with professionally administered and self-administered stress management for chemotherapy. The professional stress management consisted of a 60-minute individual educational session that included a review of common sources of chemotherapy-related stress and three specific stress-management techniques:

Paced abdominal breathing.

Progressive muscle relaxation with imagery.

The use of coping self-statements.

The professional provided the patient with an audiotape of the individual session, prescribed daily practice of the three techniques, and met briefly with the patient before his or her first chemotherapy session.

In the self-administered group, a professional met with each patient for approximately 10 minutes, provided him or her with a packet of instructional materials about coping with chemotherapy, and briefly instructed the patient on their use. These materials included all of the same information provided in the professionally administered group plus the following:

A 15-minute videotape.

A 12-page booklet.

A 35-minute relaxation audiotape.

Patients in this group were instructed to first view the videotape and then review the booklet, following its instructions for further training, practice, and use of the various techniques.

Results of this novel approach found that patients in the self-administered intervention reported significantly better physical functioning, vitality, and mental health and fewer role limitations than those reported by either of the other two groups. Patients in the professionally administered group reported no better outcomes than patients in the traditional-care group. Costs of the self-administered group were found to be significantly lower than those of the other two groups.

Brief orientation and tour of a medical oncology clinic

A novel intervention tested the effects of a brief (15- to 20-minute) clinic tour for new patients in a medical oncology clinic.[15][Level of evidence: I] The tour included the following:

An opportunity to see the phlebotomy, nursing, and chemotherapy areas.

The distribution of written materials about clinic hours and procedures.

A time to ask questions.

One hundred and fifty consecutively referred patients who had a variety of cancers were randomly assigned to either the clinic orientation condition or to standard care. Intervention patients showed less anxiety, less mood disturbance, and fewer depressive symptoms at a 1-week follow-up. In addition, these patients reported more knowledge of clinic procedures, more confidence in their physicians, and higher levels of satisfaction and hope. This is an example of how even a simple, minimal intervention can have positive benefits.

Mindfulness-based stress reduction for survivors of breast cancer

A randomized controlled trial of a 6-week mindfulness-based stress reduction intervention, compared with usual care, was conducted with 84 female survivors of breast cancer.[16] All participants were within 18 months of completion of surgery, chemotherapy, and/or radiation therapy and were thus in the transitional period from completion of active treatment to posttreatment survivorship. The intervention consisted of weekly 2-hour group sessions conducted by a psychologist who followed a standardized protocol to teach participants sitting meditation, body scan, walking meditation, and gentle yoga. All participants received a training manual and four audiotapes to support home practice and were encouraged to practice daily.

The intervention group showed improvements in psychological measures (fear of recurrence, recurrence concerns, state-trait anxiety, and depression) and quality of life (physical functioning, role limitations, and energy).

Those who practiced more frequently tended to show greater improvements.

Hypnosis and relaxation prior to excisional breast biopsy

In one study, a group of women scheduled for excisional breast biopsy (N = 90) were randomly assigned either to a brief session (15 minutes) of hypnosis and guided relaxation delivered by trained clinical psychologists on the day of surgery or to an attention-control empathic listening session of equal length. Presurgery distress was measured by the visual analog scale and the short version of the Profile of Mood States. The hypnosis session markedly decreased anticipatory anxiety and increased relaxation measured just prior to the biopsy.[17][Level of evidence: II]

Presurgical stress management in patients who are undergoing radical prostatectomy

A three-arm, randomized, controlled trial (N = 159) of a two-session (60–90 minutes) individual stress management intervention administered 1–2 weeks before radical prostatectomy for men with prostate cancer was found to have a positive impact on a number of immune system parameters (higher natural killer cell cytotoxicity and circulating proinflammatory cytokines).[18][Level of evidence: I] Statistically significant differences in immune outcomes were found only in the intervention group over a supportive attention group and a standard care group.

Improved immune outcomes were found at 48 hours postsurgery in the stress management group only.[18] A particular strength of this study is the use of a supportive attention group and a standard care group.

Use of online information

The Comprehensive Health Enhancement Support System (CHESS) [19] is an online resource for cancer patients. It has two components:

This study addressed the relative appeal and value of these two components separately for white and African American women who had been diagnosed with breast cancer (three-fourths of participants had early-stage disease). The average time spent online with either type of resource was slightly longer for African American women (didactic: 19.7 minutes, standard deviation [SD] = 31.10; narrative: 17.16 minutes, SD = 38.19) than for white women (didactic: 18.30 minutes, SD = 28.62; narrative: 15.78 minutes, SD = 36.60) but had substantially more effect.

Before using the resource, African American women were markedly lower in health care participation; after use, African American women increased health care participation markedly, regardless of type of resource, surpassing the level of health care participation by white women, particularly in regard to the effect of the didactic services. This result suggests that while the use of both the didactic and narrative CHESS resources is valuable for both groups, it is particularly useful for African American women; the narrative resource version appears to differentially have more impact for white women.

Can psychosocial interventions increase survival?

The intriguing question of whether participation in a psychosocial group intervention can result in increased survival has been investigated since 1989. The original study [20] tested a supportive-expressive group therapy format for women with metastatic breast cancer, while another study [21] tested a psychoeducational group intervention for patients with malignant melanoma. In both of these studies, a survival advantage was found in the intervention group. However, a critique of the first study [22] found that members of the control group had significantly shorter survival times than would have been expected, when compared with data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, suggesting that the survival advantages may have resulted from inadvertent sampling errors.

Attempts to replicate the supportive-expressive group therapy findings were made in Canada,[23] the United States,[24] and Australia.[25] Although all three studies found significant psychological benefits, no study could replicate the survival benefit.

Literature reviews, including three meta-analyses [26-28] and one systematic review,[29] have concluded that previous research has failed to find an effect of psychotherapy on survival. One summary [30] reported on ten additional randomized controlled trials of various psychosocial interventions for patients with various types of cancers (although most were women with breast cancer). All ten studies noted improved psychosocial benefits. However, nine of the ten showed no significant differences in survival, while one [31] found a survival advantage of about 1 year. This one positive trial was able to stratify groups on a number of important variables (e.g., nodal status, estrogen receptor and progesterone receptor status, and menopausal status) and provided data in support of possible mechanisms such as enhanced immune functioning and patient compliance with stress reduction procedures. In an analysis of results, this study identified the complexity of factors involved in any survival benefit and the possibility that immune system-mediated benefits may contribute to increased survival, when other factors are carefully taken into account.

In summary, the preponderance of evidence indicates that despite evidence of improved quality of life, it seems unlikely that a psychosocial intervention has much chance of showing an independent contribution to survival time. This evidence has caused some to suggest [32] that continued research into this question is no longer warranted.

The Adjustment Disorders

The adjustment disorders, a diagnostic category of the fourth revised edition of the American Psychiatric
Association’s Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR),[1] are defined as reactions to an identifiable psychosocial stressor
(e.g., cancer diagnosis) with a degree of psychopathology that is less severe
than diagnosable mental disorders such as major depressive disorder or
generalized anxiety disorder and yet are “in excess of what would be expected”
or result in “significant impairment in social or occupational functioning.”

Diagnostic Criteria for the Adjustment Disorders

Criterion A. The development of emotional or behavioral symptoms in response
to an identifiable stressor(s) occurring within 3 months of the
onset of the stressor(s).

Criterion B. These symptoms or behaviors are clinically significant as
evidenced by either of the following:

Marked distress that is in excess of what would be expected
from exposure to the stressor.

Significant impairment in social or occupational (academic)
functioning.

Criterion C. The stress-related disturbance does not meet the criteria for
another specific Axis I disorder and is not merely an
exacerbation of a preexisting Axis I or Axis II disorder.

Criterion D. The symptoms do not represent bereavement.

Criterion E. Once the stressor (or its consequences) has terminated, the
symptoms do not persist for more than an additional 6 months. Specify:

Prevalence

In the general population, adjustment disorders are thought to be common,
although prevalence rates vary by population studied. In studies of community
samples of children, adolescents, and the elderly, prevalence estimates have
ranged from 2% to 8%. In outpatient mental health settings, prevalence rates
have been as high as 10% to 30%; while in general hospital inpatients,
prevalence rates have been as high as 12% of those referred for a mental health
consultation.[1]

Nearly every cancer patient experiences what could be considered an
identifiable stressor, whether that is diagnosis, treatment, recurrence, or
side effects. The presence of an adjustment disorder is determined more by the
patient’s response to the identifiable stressor, and whether that response is
considered in excess of what would be expected or results in significant
impairment, typically in social or occupational functioning.

One study [2] evaluated 215 randomly selected hospitalized and ambulatory
cancer patients in three different cancer centers and found that of this group,
slightly fewer than half (47% or 101 patients) met the diagnostic criteria for
any mental disorder (DSM-III criteria). From this group of 101, 68% (69
patients) met the diagnostic criteria for an adjustment disorder. Of the
entire 215 patients evaluated, approximately 32% were identified as meeting the
diagnostic criteria for an adjustment disorder—the highest prevalence of any
diagnostic category.

Additional reviews [3] have continued to find adjustment disorders to be the most common mental disorder. In patients with advanced cancer, prevalence ranges from 14% to 34.7%; in terminally ill patients, rates range from 10.6% to 16.3%. These variable prevalence rates are influenced by stage of disease, type of cancer, diagnostic procedures used, and other patient variables. In a study of women with breast cancer undergoing adjuvant chemotherapy, a 36.1% prevalence rate was found.[4]

In another study of terminally ill Japanese cancer patients referred to a palliative care unit, 16.3% were diagnosed with an adjustment disorder at the time of their initial referral, and 10.6% were diagnosed with an adjustment disorder at the time of their admission to the palliative care unit. Of patients diagnosed with adjustment disorder at initial referral, 42% had progressed to major depression at admission to the unit, and 42% had no diagnosis.[5]

Adjustment disorders
are the most commonly diagnosed mental disorder in the oncology setting.

Course

As defined in the diagnostic criteria, an adjustment disorder begins within 3
months of the onset of an identifiable stressor and lasts no longer than 6
months after the stressor or its consequences have ceased. Two specifiers
exist to discriminate between an acute adjustment disorder (≤6
months) and a chronic adjustment disorder (>6 months). The cancer
patient may experience a sequence of multiple, sequential stressors such as the
diagnosis, the start of treatment, side effects of treatment, conclusion of
treatment, and return to work.

It is often difficult to determine when a
stressor has ceased. It is not unusual to see a chronic adjustment disorder
that persists because of the presence of multiple, sequential stressors. The
persistent adjustment disorder may also progress to become a more serious
mental disorder (e.g., major depressive disorder). Chronic adjustment
disorders that persist and progress to more severe mental disorders appear more
common in children and adolescents than in adults.[1] (Refer to the PDQ summary on Pediatric Supportive Care for more information.)

Problems in Diagnosing Adjustment Disorders

The adjustment disorders are an intermediate category between normal adjustment
and a specific diagnosable mental disorder. In terms of their location within
a hierarchy of increasingly severe mental disorders, the adjustment disorders
are an intermediate category as follows:

Screening instruments for the identification of adjustment disorder have been difficult to identify.[7,8] This intermediate status and the lack of any specific list of symptoms raise a
number of problems with the adjustment disorder’s diagnostic category.[6] Most
of the problems stem from lack of specificity and resulting subjectivity. This
lack of specificity applies to both the identifiable stressor and the marked
distress/significant impairment.

No criteria or guidelines exist in DSM-IV-TR to quantify the nature of the
psychosocial stressor(s). Given individual differences in coping abilities,
certain stressors are likely to be very stressful for one patient and not
stressful at all for another patient. With no quantifiable guidelines for
measuring stressors, a diagnosis is often determined by the nature of an
individual’s response. If a person responds with marked distress or
significant impairment in functioning, it is often assumed that the life event
was an identifiable stressor. However, the identification of a response that
evidences marked distress or significant impairment also lacks specificity and
is thus very subjective. Many of these diagnostic terms are too vague to be
valid or reliable; thus, there is considerable variation in the use of the
adjustment disorder category.

Despite these problems, the adjustment disorder category does provide a means
of identifying an emotional or behavioral response in need of further
treatment. Cancer patients are regularly confronted with a variety of
stressors and thus face the potential of experiencing an adjustment disorder.

Treatment

Individual and group counseling and psychotherapy

Although only one study has been targeted specifically at a population of cancer
patients diagnosed exclusively with adjustment disorder, a number of studies
have shown the benefits of psychosocial interventions with adult cancer
patients (e.g., meta-analysis).[9][Level of evidence: I] These interventions have included both
individual [10][Level of evidence: I] and group counseling [11][Level of evidence: IV];[12,13][Level of evidence: I] and have utilized a variety of
theoretical approaches.
In a randomized clinical trial for the treatment of adjustment disorders, 57 patients with mixed cancer types were randomly assigned to either an 8-week individual, problem-focused, cognitive-behavioral psychotherapy intervention or an 8-week individual, supportive counseling intervention.[14][Level of evidence: I] Results showed that those receiving the problem-focused, cognitive-behavioral therapy exhibited a significant change in fighting spirit, coping with cancer, anxiety, and self-defined problems, both at the conclusion of the intervention and at the 4-month follow-up.

Cognitive-behavioral interventions have been widely studied. A
cognitive-behavioral approach is based on the idea that mental, emotional, and
even physical symptoms partly stem from one’s thoughts, feelings, and
behaviors, resulting in poor adaptation.[15] Interventions focus directly on a
patient’s thoughts, feelings, and behaviors with the goal of altering specific
coping strategies and alleviating emotional distress. Cognitive-behavioral
interventions include a variety of techniques such as:

Most studies have combined a
variety of these approaches into a multicomponent treatment strategy designed
to alleviate specific symptoms. Cognitive-behavioral approaches tend to be
relatively short-term, brief interventions, well-suited to the oncology
setting.[15,16] One study [17][Level of evidence: I] randomly assigned 382 patients with different types of cancer to one of three groups: usual care, professionally led stress management, or self-administered stress management. The two intervention groups received stress management training that included abdominal breathing, progressive muscle relaxation training with guided imagery, and coping self-statements prior to the start of chemotherapy. The professionally led intervention group met with a mental health professional who taught them the stress management skills in one 60-minute session. The self-administered group received a packet of training materials that included a 15-minute videotape of instructions, a 12-page booklet on coping with chemotherapy, and a 35-minute audiotape of relaxation training instructions. Results showed enhanced quality of life over usual care in the self-administered group only. The professionally led group did not show any improvement in quality of life when compared with usual care.

A meta-analysis of 45 such studies investigating 62 treatment-control
comparisons found significant beneficial effects in emotional adjustment.[9][Level of evidence: I]
Beneficial effect sizes for emotional adjustment ranged from .19 to .28,
indicating that the average cancer patient receiving treatment was better off
than 56.5% to 59.5% of those patients not receiving treatment. These
interventions have been administered in both individual [10][Level of evidence: I] and group
formats,[18][Level of evidence: II] indicating benefits in emotional adjustment from both formats at
the conclusion of the intervention and at 6-month and 12-month follow-up
assessments. One novel approach adapted a 6-week group format to a telephone conference call structure for breast cancer survivors; there was high acceptability and modest treatment effects immediately after the intervention but not at the 3-month follow-up.[19][Level of evidence: I]

Another study found that a cognitive behavioral intervention to teach problem solving was effective in promoting better self-management of cancer-related symptoms, especially for patients aged 60 years or younger.[20][Level of evidence: I]

Pharmacotherapy

No studies have specifically targeted a population of cancer patients diagnosed
exclusively with adjustment disorder, in which the primary intervention was some
form of pharmacotherapy. Given the nature of the adjustment disorders,
clinical experience suggests that, if available, an initial trial of short-term counseling or
psychotherapy designed to alter or eliminate the identified stressor (and thus
alleviate symptoms) should be tried before pharmacotherapy.[6]

As mentioned
previously, sometimes the adjustment disorder may progress to a more severe
mental disorder (e.g., major depressive disorder) and thus warrant
consideration of pharmacotherapy. In addition, when the patient does not
benefit from short-term psychotherapy, adding an appropriate psychotropic
medication for a brief period of time (e.g., 2–3 weeks for antianxiety
medications, 12 months for antidepressants) may facilitate the psychotherapy,
allowing the patient to better employ available coping strategies. The
specific pattern of emotional or behavioral symptoms will determine which type
of psychotropic medication to consider. (Refer to the PDQ summary on
Depression for more information.)

Current Clinical Trials

Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about
adjustment disorder that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Anxiety Disorders: Description and Etiology

Anxiety occurs to varying degrees in patients with cancer and may increase as
the disease progresses or as treatment becomes more aggressive.[1]
Investigators have found that 44% of patients with cancer reported some
anxiety, and 23% reported significant anxiety.[2,3]

Anxiety can be part of normal
adaptation to cancer. In most cases, the reactions are time limited and may
motivate patients and families to take steps to reduce anxiety (e.g., gain
information), which may assist in adjusting to the illness. However, as discussed above, anxiety
reactions that are more prolonged or intense are classified as adjustment
disorders. These disorders can negatively affect quality of life and interfere
with a cancer patient’s ability to function socially and emotionally. These
anxiety reactions require intervention.[4] Anxiety disorders may also be secondary to other aspects of the medical condition, such as uncontrolled pain, certain metabolic states, or medication side effects.

Other specific anxiety disorders—such as generalized anxiety, phobia, or panic disorder—are not as common among
cancer patients and usually predate the cancer diagnosis, but deserve further attention to facilitate cancer care. The stress caused by
a diagnosis of cancer and its treatment may precipitate a relapse of pre-existing anxiety disorders. These disorders can be disabling and can interfere
with treatment. They require prompt diagnosis and effective management.[5]

Factors that can increase the likelihood of developing anxiety disorders
during cancer treatment include the following:

Some medical
conditions and interventions are associated with symptoms that present as anxiety disorders, including central
nervous system metastases, dyspnea associated with lung cancer, and treatment with corticosteroids and
other medications. A patient’s experience with cancer or other illnesses may
reactivate associations and memories of previous illness and contribute to
acute anxiety. Certain demographic factors, such as being female and
developing cancer at a young age, are associated with increased anxiety in
medical situations.[2,8] Patients who have problems communicating with their
families, friends, and physicians are also more at risk of developing
anxiety.[8]

Anxiety, on the other hand, can lead to overestimation of negative prognosis. A longitudinal study of women with ductal carcinoma in situ (N = 487) found that anxiety as measured by the Hospital Anxiety and Depression Scale was the factor that was most consistently and strongly associated with inaccurate perception of and overestimation of future breast cancer–related risks.[9]

In the patient with advanced disease, anxiety is often not caused by the fear
of death but by the issues of uncontrolled pain, isolation, abandonment, and
dependency.[10] Many of these factors can be managed when adequately assessed
and properly treated.

Anxiety Disorder Caused by Other General Medical Conditions

The following table highlights possible causes of anxiety in cancer patients.

Corticosteroids, neuroleptics used as antiemetics, thyroxine, bronchodilators, beta-adrenergic stimulants, antihistamines, and benzodiazepines (paradoxical reactions are often seen in older persons).

Anxiety-producing conditions

Substance withdrawal (from alcohol, opioids, or sedative-hypnotics).

Patients in severe pain are
anxious and agitated, and anxiety can potentiate pain. To adequately manage
pain, the patient’s anxiety must be treated.[12,13]

Acute onset of anxiety may be a precursor of a change in metabolic state or of
another impending medical event such as myocardial infarction, infection, or
pneumonia. Sepsis and electrolyte abnormalities can also cause anxiety
symptoms. Sudden anxiety with chest pain or respiratory distress may suggest a
pulmonary embolism. Patients who are hypoxic can experience anxiety; they may
fear that they are suffocating.

Many drugs can precipitate anxiety in persons who are ill. For example,
corticosteroids can produce motor restlessness, agitation, and mania as well as
depression and thoughts of suicide. Bronchodilators and B-adrenergic receptor
stimulants used for chronic respiratory conditions can cause anxiety,
irritability, and tremulousness. Akathisia, motor restlessness accompanied by
subjective feelings of distress, is a side effect of neuroleptic drugs, which
are commonly used for control of emesis. Withdrawal from opioids,
benzodiazepines, barbiturates, nicotine, and alcohol can result in anxiety,
agitation, and behaviors that may be problematic for the patient who is in
active treatment.

Certain tumor sites can produce symptoms that resemble anxiety disorders.
Pheochromocytomas and pituitary microadenomas can present as episodes of panic
and anxiety.[14] Non–hormone-secreting pancreatic cancers can cause anxiety
symptoms. Primary lung tumors and lung metastases can often cause shortness of
breath, which can lead to anxiety.

Primary Anxiety Disorders

Patients who have the following symptoms may be experiencing a specific anxiety
disorder that was present before they became ill with cancer and that recurs
because of the stress of the diagnosis and treatment:

Intense fear.

Inability to absorb information.

Inability to cooperate with medical
procedures.

Somatic symptoms include the following:

Shortness of breath.

Sweating.

Lightheadedness.

Palpitations.

Patients with cancer can present with the
following anxiety disorders:

Phobias.

Panic disorder.

Generalized
anxiety disorder.

Obsessive-compulsive disorder.

Adjustment disorder.

Post-traumatic stress disorder.

Anxiety disorder that is caused by other general medical
conditions.

Patients with these anxiety disorders are generally distressed about their symptoms and
are usually compliant with behavioral and psychopharmacologic intervention.[4]

Phobias

Phobias are persistent fears or avoidance of a circumscribed object or
situation. People with phobias usually experience intense anxiety and avoid
potentially frightening situations. Phobias are experienced by cancer patients
in a number of ways, such as fear of witnessing blood or tissue injury (also
known as needle phobia) or claustrophobia (for example, during a magnetic resonance imaging scan).
Phobias can complicate medical procedures and can result in the refusal of
necessary medical intervention or tests.[4]
Phobias generally respond well to exposure therapy and cognitive behavioral therapy (CBT).

Panic disorder

In panic disorder, intense anxiety is the predominant symptom, virtually always accompanied by severe somatic
symptoms that include the following:

Shortness of breath.

Dizziness.

Palpitations.

Trembling.

Diaphoresis.

Nausea.

Tingling sensations.

Fears of
going crazy or that a heart attack is occurring.

Panic disorder is characterized by discrete panic “attacks” that are experienced as happening suddenly, often without a specific trigger, and become intense very quickly. Attacks or discrete periods of intense discomfort generally last for
several minutes or longer, but the discomfort generally lasts for hours. A common complication is agoraphobia or avoidance of open places, caused by fear of situations that might trigger attacks. Patients with panic attacks often present with
symptoms that can be difficult to differentiate from other medical disorders,
though a known history of panic disorder can help clarify the diagnosis. Panic
disorder in patients with cancer is most often managed with benzodiazepines and
antidepressant medications [4] but also responds well to CBT.

Generalized anxiety disorder

Generalized anxiety disorder is characterized by ongoing, unrealistic, and
excessive anxiety and worry about two or more life circumstances, to a degree that is pervasive and does not respond to either reassurance or contrary evidence. The following physical symptoms may be reported but do not have the sudden onset or intensity of panic attacks:

Vigilance in scanning (feeling keyed up and on edge, irritability, and having exaggerated startle responses).

Some examples
of generalized anxiety disorder are patients’ fears that no one will care for them, even though they have
adequate and willing social support; and the fear of exhausting their finances,
even though adequate insurance and financial coverage is available. Frequently,
a generalized anxiety disorder is preceded by a major depressive episode.

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is characterized by persistent thoughts, ideas,
or images (obsessions) and by repetitive, purposeful, and intentional behaviors
(compulsions) that a person performs to manage his or her intense distress.
To qualify as OCD, the obsessive thoughts and
compulsive behaviors must be time-consuming and sufficiently distracting to
interfere with the person’s ability to function in employment, academic, or
social situations.

Patients with cancer who have a history of OCD may engage in compulsive behaviors such as hand washing,
checking, or counting to such an extent that they cannot comply with treatment.
For such patients, normal worry about the cancer diagnosis and prognosis can
develop into full obsessive-compulsive symptoms and be severely disabling.
OCD is most often managed with serotonergic
antidepressant medications (selective serotonin reuptake inhibitors [SSRIs] and
clomipramine) and CBT. Milder obsessive thoughts or use of rituals that are not interfering might be addressed with CBT, but medications are not indicated. This disorder is rare in
cancer patients who do not have a premorbid history.

Screening and Assessment

Effective management of anxiety disorders begins with a thorough and
comprehensive assessment and an accurate diagnosis. The normal fears and
uncertainties associated with cancer are often intense. Frequently not clear is the distinction between normal fears and fears that are more
severe and reach the criteria for an anxiety disorder (see Table 3 for more information).[11]

Treatment
should consider the patient’s quality of life, not be based solely on the disorder. To assess the severity
of the anxiety, it is important to understand to what extent the symptoms of
anxiety are interfering with activities of daily living. Screening for anxiety could include a brief self-report questionnaire that, if a defined cutoff score is exceeded, could then be followed by a more thorough clinical interview. A variety of general screening questionnaires have been used for identification of distress. (Refer to the section on Self-report screening instruments in this summary for more information.) Other anxiety-specific self-report questionnaires (e.g., State-Trait Anxiety Inventory) have also been used, and a questionnaire for the assessment of prostate cancer–related anxiety has been developed and validated.[2,15,16]

The following is a list of symptoms designed to distinguish common or normal worry from more serious symptoms of anxiety. When patients are reporting the more serious symptoms, referral to a qualified mental health professional may be warranted.

Interventions

When anxiety is
situational (i.e., produced by pain, another underlying medical condition, a
hormone-secreting tumor, or a side effect of medication), the prompt treatment
of the cause usually leads to immediate control of the symptoms.[1] Some
effective coping strategies include encouraging fearful patients to:[18]

Confront
the problem directly.

Try to view the situation as a problem to be solved or
as a challenge.

Try to obtain complete information.

Try to be flexible
(taking things as they come).

Think of major events as a series of step-by-step tasks.

Use resources and support.

Initial management of anxiety includes providing adequate information and
support to the patient. Initial symptoms, which may warrant a psychiatric or psychological consultation, may first be reported to the primary oncologist or surgeon.[19][Level of evidence: IV]

Combining different approaches can be beneficial for some patients. (Refer to the Psychosocial Interventions for Distress section of this summary for more information.) Individuals who may be struggling with anxiety disorders should be referred for full assessment and psychological treatment.

One study of 509 recurrence-free breast cancer survivors at 5 to 9 years posttreatment examined the usefulness of a comprehensive intervention that combined positive coping strategies based on CBT (e.g., calming self-talk or relaxation) with education about the disease, treatment, and potential side effects.[21] Findings from this study indicate that women in the intervention group (n = 244) regularly used the intervention components to deal with triggers of fears of breast cancer recurrence and long-term treatment side effects. Most women in the intervention group found the strategies very helpful.[21][Level of evidence: I]

Preliminary evidence suggests racial differences in the use and benefit of specific coping strategies (e.g., religious coping strategies such as prayer and hopefulness are used more by African American women and provide greater benefit for these women).[21][Level of evidence: I];[22][Level of evidence: II]

Pharmacologic interventions

Patients with cancer often have symptoms of both anxiety and depression that
are caused by stressors related to cancer treatment. Such symptoms of distress often are
resolved with psychologic support alone. However, in some cases, pharmacologic interventions are required to address these symptoms. (Refer to Table 3 for descriptions of symptoms of anxiety disorders possibly requiring pharmacological treatment.)

Following are brief descriptions of pharmacological treatment options and potential indications for their use. These descriptions are based on evidence derived from studies conducted in patients without cancer because of the lack of such studies in patients with cancer. However, it is important to note that clinicians have used some of these medications for several decades to treat anxiety symptoms in patients with cancer. The treatment options and their use in the situations described below are also based on clinical experience with these agents in patients with cancer.

The use of medications to treat anxiety disorders is considered when patients are experiencing more severe symptoms or when their responses to psychosocial interventions are inadequate. When counseling resources are not available or are declined by the patient, medication may be considered sooner rather than later. In certain cases, medications are started simultaneously with psychosocial interventions when it is likely that psychosocial support alone will be inadequate to provide relief or to provide it soon enough.

Pharmacological interventions can be used short-term or long-term, depending on individual patient and illness factors, including the following:

Specific anxiety medications—i.e., medications from the benzodiazepine class, as listed in Table 4—are frequently used alone or in combination with psychological approaches to provide relief from anxiety symptoms. These medications are effective in the acute treatment of anxiety disorders because of their rapid onset of action. They are frequently used as monotherapy or as adjunctive agents in the short-term management (<4 months) of anxiety disorders. Their long-term use (>4 months) is limited by the potential for abuse and dependence and by their lack of antidepressant effects, as depression is often comorbid with anxiety disorders. Following are some of the indications and safety considerations for the use of benzodiazepines in patients with cancer:[23,24]

Short-acting benzodiazepines such as alprazolam and lorazepam can be effectively used to provide short-term relief at specific points in the cancer continuum of diagnosis, treatment, and recurrence. Examples of such short-term use include the treatment of anxiety during diagnostic procedures (e.g., certain radioimaging procedures) and the treatment of patient anxiety about pending test results (e.g., for yearly mammograms in patients with histories of breast cancer).

Longer-acting medications (e.g., diazepam and clorazepate) should generally be avoided because of their long half-lives. These medications can cause or exacerbate cognitive impairment, disorientation, and drowsiness because of their potential for accumulation.

Patients with medical conditions such as delirium can present with anxiety and agitation. Benzodiazepine use in patients with such conditions is counterindicated because these agents can cause or exacerbate confusion and disorientation.

All patients, especially elderly patients, receiving benzodiazepines should be closely monitored for cognitive impairment, daytime sedation, and fall risks. Use of these agents should be optimized in elderly patients, patients with multiple comorbidities, patients with liver disease, and patients receiving multiple medications.

Use of these agents should be closely monitored and optimized in patients receiving other sedating medications, central nervous system depressants, and agents with potential for causing respiratory depression (e.g., opiates).

It is important to continuously monitor and reevaluate anxiety symptoms in all patients receiving benzodiazepines. Use of these medications can be tapered off if anxiety symptoms resolve with the conclusion of cancer treatments.

In some patients, the use of benzodiazepines is continued (as monotherapy or as adjunctive treatment) over a longer period (>4 months) because of persistent and debilitating anxiety symptoms. It is important to monitor the development of tolerance, abuse, and dependence issues as well as comorbid depressive symptoms in such patients. Long-term and sometimes chronic use of these agents might be indicated in a subpopulation of patients, with close monitoring and frequent risk-benefit assessments. Persistent (after 3 or 4 months) anxiety symptoms frequently lead to depression. Patients with persistent anxiety symptoms with or without depression might benefit from alternative treatments (e.g., paroxetine, sertraline).

Table 4. Commonly Prescribed Benzodiazepines in Cancer Patientsa

Drug Equivalent

Approximate Oral Dose (mg)b

Initial Dose (mg)

Elimination Half-life of Drug Metabolites (h)

bid = twice a day; qd = once a day; qid = 4 times a day; tid = 3 times a day.

bRefer to the PDQ summary on Depression for dosing information on antidepressants used for anxiety as described in this summary.

Short acting

Alprazolam (Xanax)

0.5

0.25–2.0 tid–qid

10–15

Oxazepam (Serax)

10.5

10–15 tid–qid

5–15

Lorazepam (Ativan)

1.0

0.5–2.0 tid–qid

10–20

Temazepam (Restoril)

15.0

15–30 at bedtime

10–15

Intermediate acting

Alprazolam (Xanax XR)

1.0

1–6 qd

10–15

Clonazepam (Klonopin)

1.0

0.5–2.0 bid–tid

19–50

Long acting

Chlordiazepoxide
(Librium)

10.0

10–50 tid–qid

10–40

Diazepam (Valium)

5.0

5–10 bid–qid

20–100

Clorazepate (Tranxene)

7.5

7.5–15.0 bid

30–200

The choice of a benzodiazepine depends on the following:

Duration
of action that is best suited to the patient.

Desired rapidity of onset
needed.

Route of administration available.

Presence or absence of
active metabolites.

Metabolic problems.

Dosing schedules depend on patient
tolerance and require individual titration. The shorter-acting benzodiazepines
(alprazolam and lorazepam) are given 3 to 4 times per day. Short-acting
benzodiazepines, particularly those that can be administered by multiple routes
(lorazepam and diazepam), are effective for high levels of distress.
Benzodiazepines decrease daytime anxiety and reduce insomnia. (Refer to the
PDQ summary on Sleep Disorders for more information.) The most common side
effects of benzodiazepines are dose dependent and are controlled by titrating
the dose to avoid drowsiness, confusion, motor incoordination, and sedation.

All benzodiazepines can cause some degree of respiratory depression, which is generally minimal in patients who have not used benzodiazepines in the past. Benzodiazepines should be used cautiously (or not at all) in cases of respiratory impairment.

Standard precautions should be considered when any sedative drug is used in patients who have borderline respiratory function. Ongoing assessment of this population is important. Low doses of the antihistamine hydroxyzine (25 mg, 2–3 times a day) can be used safely in such situations. In patients with hepatic dysfunction, it is best to use short-acting benzodiazepines that are metabolized primarily by conjugation and excreted by the kidneys (e.g., oxazepam, temazepam, or lorazepam). Another advantage of using lorazepam is its lack of active metabolites. Conversely, other benzodiazepines should be selected in cases of renal dysfunction.

SSRIs (e.g., fluoxetine and sertraline) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., venlafaxine) are considered first-line pharmacotherapy for long-term management of anxiety disorders. SSRIs and SNRIs are also effective in the treatment of depressive symptoms frequently comorbid with persistent anxiety disorders. SSRIs and SNRIs can take approximately 4 to 6 weeks to take effect because of their slow onset of action. Benzodiazepines are frequently used as adjunctive agents to stabilize symptoms in the initial period of treatment with SSRIs and SNRIs.

Atypical antidepressants (e.g., mirtazapine) are sometimes used to treat anxiety disorders because of their added effects on comorbid symptoms such as insomnia. Older medications such as tricyclic antidepressants (e.g., imipramine and clomipramine) and monoamine oxidase inhibitors (e.g., phenelzine) are also effective in treating anxiety disorders. The use of antidepressants in clinical practice is limited by their unfavorable side effects, poorer tolerability, and higher risks of toxicity.[26]

Buspirone, a nonbenzodiazepine, is useful in patients who have not previously
been treated with a benzodiazepine and in those who may abuse benzodiazepines
(e.g., those with a history of illicit substance abuse or alcoholism).
Buspirone is also useful in the geriatric population to augment fluoxetine for the treatment of anxiety and depression. The beginning dose is
5 mg 3 times a day and can be increased to 15 mg 3 times a day.
Buspirone can also be given twice a day.

The use of specific classes of medications is considered for managing treatment-refractory anxiety symptoms or in certain special clinical situations. Low-dose neuroleptics (e.g.,
thioridazine, 10 mg 3 times a day; and risperidone, 1 mg twice a day) are used to treat severe anxiety
when an adequate dose of a benzodiazepine is ineffective or if the patient
might be expected to respond poorly to benzodiazepines (e.g., patients with
brain metastases). Low-dose neuroleptics can also be used when benzodiazepines
are not helpful or when there is the possibility of delirium, dementia, or
other complications. Low-dose anticonvulsants (e.g., pregabalin, 200 mg per day) are sometimes used to treat severe treatment-resistant anxiety when other medications are ineffective or contraindicated because of certain associated risks.[26] Generally, the use of neuroleptics or anticonvulsants is considered after adequate trials with several first-line agents (e.g., SSRIs, SNRIs, and benzodiazepines) because of the significant side effect burden and potential for drug-drug interactions with these agents. Consultation with a psychiatric clinician is strongly recommended before these medications are used. Direct involvement of a psychiatric clinician is imperative for the management of patients receiving these medications.

The presence or absence of specific psychiatric or medical comorbidities is frequently a critical factor in the selection of pharmacological treatments. Pharmacokinetic and pharmacodynamic interactions with other medications are also important factors to be considered in the selection of agents. Following are some examples of such factors and clinical situations driving the selection of pharmacological treatments:

When depressive symptoms are comorbid with anxiety, treatment with SSRIs, SNRIs, or other antidepressants is strongly considered.

When neuropathic pain is comorbid with anxiety symptoms, specific antidepressants with known efficacy in treating neuropathic pain (e.g., duloxetine and venlafaxine) are considered.

When hot flashes are comorbid with anxiety symptoms, specific agents with known efficacy in treating hot flashes (e.g., venlafaxine) are considered.

Specific medications with known side effects (e.g., nausea with duloxetine or risk of sedation with mirtazapine) are avoided when patients are already experiencing these side effects from their cancer treatments and because of the possible exacerbation of these side effects.

Patients who are treated with CYP2D6 inhibitors (e.g., paroxetine) and tamoxifen may be at risk of significant drug-drug interactions. (Refer to the PDQ summary on Hot Flashes and Night Sweats for more information.)

No pharmacological treatment studies have been conducted in children and adolescents with cancer. Furthermore, evidence on pharmacological treatment of anxiety disorders in pediatric patients without cancer is also limited. One meta-analysis of pediatric antidepressant clinical trials [27][Level of evidence: I] found antidepressants efficacious relative to placebo in the treatment of anxiety disorders, with strongest effects in non-OCD anxiety disorders (e.g., generalized anxiety disorder or social anxiety disorder) and intermediate effects in OCD. (Refer to the PDQ summary on Depression for a discussion of the risk of suicidal ideation/suicide attempt associated with antidepressant use.)

In general, patients with cancer need to be encouraged to take enough medication to relieve anxiety. Medications are readily tapered and
discontinued when symptoms subside. Concerns about addiction are exaggerated
in patients with cancer and often interfere with adequate symptom relief.

Current Clinical Trials

Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about
anxiety disorder that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about normal adjustment issues, and the pathophysiology and treatment of psychosocial distress and the adjustment disorders. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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